Higher‐order of chronic lymphocytic leukaemia (CLL) classification: shared antigenic specificities of stereotyped B‐cell receptor subsets as defined by the European Research Initiative on CLL consortium

Bende, Richard J.; Janssen, Jeroen; Noesel, Carel J.M. van

doi:10.1111/bjh.17964

Cited by 1 publication

(3 citation statements)

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“…The IgMs of OM8 and OAMZL3 were not encoded by stereotyped RF IGHV rearrangements, whereas OAMZL44 expressed the here newly defined stereotyped RF IGHV3-74/IGKV4-1 combination. RF mono-reactivity has previously also been demonstrated by us for an immunological subset of M-CLL ( Hoogeboom et al, 2013b ; Janssen et al, 2021 ; Bende et al, 2022 ). However, in contrast to our previous findings on subsets of M-CLL, we did not observe binding of OAML IgMs with any viral, bacterial, or fungal antigens ( Hoogeboom et al, 2013a ; Bende et al, 2022 ).…”

Section: Discussionmentioning

confidence: 54%

“…The OAML-derived VH-CDR3 amino acid (aa) sequences were analyzed for homology with VH-CDR3 aa sequences present in GenBank (release 244), using the NCBI Protein-BLAST algorithm. VH-CDR3s were defined as being homologous when they shared at least 60% amino acid sequence homology, with an allowed maximal gap of three amino acids (Tables S3 and S4) ( Bende et al, 2016 , 2020 , 2022 ).…”

Section: Resultsmentioning

confidence: 99%

“…The level of poly-reactivity of the three OAML IgMs, however, was substantially lower than that of two selected poly-reactive IgMs retrieved from U-CLLs. Six of the 124 OAML IGHVs (5%) were stereotyped high affinity RFs ( Bende et al, 2005 , 2016 , 2020 , 2022 ; Hoogeboom et al, 2010 , 2013b ; Janssen et al, 2021 ). Three of the produced 23 (13%) OAML IgMs displayed strong mono-reactive RF activity in an IgG ELISA.…”

Section: Discussionmentioning

confidence: 99%

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Distinct groups of autoantigens as drivers of ocular adnexal MALT lymphoma pathogenesis

Bende,

Donner,

Wormhoudt

et al. 2024

Life Sci. Alliance

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Chronic B-cell receptor signals incited by cognate antigens are believed to play a crucial role in the pathogenesis of mucosa-associated lymphoid tissue lymphomas. We have explored the immunoglobulin variable regions (IGHV) expressed by 124 ocular adnexal MALT lymphomas (OAML) and tested the in vitro reactivity of recombinant IgM derived from 23 OAMLs. Six of 124 OAMLs (5%) were found to express a high-affinity stereotyped rheumatoid factor. OAMLs have a biased IGHV4-34 usage, which confers intrinsic super auto-antigen reactivity with poly-N-acetyllactosamine (NAL) epitopes, present on cell surface glycoproteins of erythrocytes and B cells. Twenty-one OAMLs (17%) expressed IGHV4-34-encoded B-cell receptors. Five of the 23 recombinant OAML IgMs expressed IGHV4-34, four of which bound to the linear NAL i epitope expressed on B cells but not to the branched NAL I epitope on erythrocytes. One non-IGHV4-34-encoded OAML IgM was also reactive with B cells. Interestingly, three of the 23 OAML IgMs (13%) specifically reacted with proteins of U1-/U-snRNP complexes, which have been implicated as cognate-antigens in various autoimmune diseases such as systemic lupus erythematosus and mixed connective tissue disease. The findings indicate that local autoimmune reactions are instrumental in the pathogenesis of a substantial fraction of OAMLs.

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